Changes in Levels of Biomarkers Associated with Adipocyte Function and Insulin and Glucagon Kinetics During Treatment with Dapagliflozin Among Obese Type 2 Diabetes Mellitus Patients

Aki Okamoto, Hirohide Yokokawa, Hironobu Sanada, Toshio Naito, Aki Okamoto, Hirohide Yokokawa, Hironobu Sanada, Toshio Naito

Abstract

Objectives: This study aimed to investigate changes in levels of biomarkers associated with adipocyte function and insulin and glucagon kinetics after a meal tolerance test (MTT) during treatment with dapagliflozin among obese type 2 diabetes mellitus (T2DM) patients.

Methods: T2DM patients with hemoglobin A1c (HbA1c) levels >6.5 % and body mass index (BMI) >25 kg/m2 were treated with dapagliflozin 5 mg/day for at least 12 weeks. HbA1c, body weight, ketone bodies, adiponectin, plasminogen activator inhibitor-1 (PAI-1), and C-reactive protein (CRP) were measured before and after treatment with dapagliflozin. A subset of patients underwent an MTT.

Results: Of 27 participating patients (mean age 47.9 years; 17 males), five were drug-naive and 22 were treated with other antidiabetic agents, including insulin and glucagon-like peptide-1 (GLP-1) receptor agonists. Following treatment with dapagliflozin, HbA1c levels significantly improved (7.44 ± 0.56 to 6.70 ± 0.0.57 %; p < 0.01), body weight significantly decreased (90.9 ± 16.5 to 87.1 ± 15.9 kg; p < 0.01), ketone bodies increased, adiponectin significantly increased, and high-sensitivity CRP tended to decrease. During the MTT, blood glucose ΔAUC2 significantly decreased, glucagon ΔAUC2 increased, and immunoreactive insulin (IRI) did not change in 11 of 27 patients.

Conclusion: Although ketone bodies increased significantly, adiponectin increased and high-sensivity CRP decreased significantly. These findings suggest that sodium-glucose cotransporter-2 (SGLT2) inhibitors may potentially improve adipocyte function in treating obese T2DM patients.

Conflict of interest statement

Compliance with Ethical Standards The study has not received any funding. A.O., H.Y., H.S., and N.T. declare no conflict of interest. The study protocol was reviewed and approved by the Council of Okamoto Medical Clinic. All procedures followed were in accordance with ethical standards of the responsible committees on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 and 2008. Informed consent was obtained from all patients in the study.

Figures

Fig. 1
Fig. 1
Changes in a glucose, b insulin, and c glucagon levels after the meal tolerance test

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